Ultrasound Diagnosis of Placental and Umbilical Cord Anomalies in Singleton Pregnancies Resulting From In-vitro Fertilization (PLACENTA)

Ultrasound Diagnosis of Placental and Umbilical Cord Anomalies in Singleton Pregnancies Resulting From In-vitro Fertilization: a Prospective Cohort Study

Objectives: to identify which type of placental and umbilical cord abnormalities are more common in IVF singleton pregnancies; to investigate if heterologous fertilization is an additional risk factor for the development of these abnormalities.

Methods: this was a multicenter prospective cohort study study involving two tertiary centres (S. Orsola Hospital, University of Bologna and Institute for Women's Health, University College of London). Patients with a singleton pregnancy conceived with IVF were consecutively recruited between May 2019 to January 2021. Each case was matched with a control presenting with a spontaneous pregnancy during the same period of time. All patients underwent similar antenatal care, which included ultrasound examinations at 11-14, 19-22 and 33-35 weeks. Ultrasound findings of placental and/or umbilical cord abnormalities were recorded in the two groups and confirmed after birth. The incidence of placental/cord findings in the study group was assessed using the chi-squared test or Fisher's exact test, where appropriate. Post-hoc pairwise comparisons were performed with the Fisher's exact test, using the Simes' method for false discovery rate control.

Study Overview

• Status: Completed
• Conditions: Placenta Diseases; IVF
• Intervention / Treatment: Diagnostic test: ultrasound according routine antenatal care

Detailed Description

This was a multicenter prospective cohort study study involving two tertiary centres (S. Orsola Hospital, University of Bologna and Institute for Women's Health and University College of London). All patients with a singleton pregnancy conceived with IVF were consecutively recruited between 1st of May 2019 to 31st March 2021. Each case was matched with a control presenting with a SC during the same period of time.

All patients had antenatal care using a similar clinical protocol, which included at 11-14 weeks (nuchal thickness screening scan), 19-22 weeks (detailed fetal anatomy scan) and 33-35 weeks (growth scan). All ultrasound examinations are carried out transvaginally and/or transabdominally by experienced operators using a high-resolution ultrasound equipment. Ultrasound findings of placental and/or umbilical cord abnormalities were recorded in each case using a standardized reporting protocol including placental location, cord insertion. The placenta was recorded as "low lying" when the edge was 0.5-2 cm from the internal os of the uterine cervix. When the placenta was <0.5cm from the internal os or completely covering it, it was defined as placenta previa (marginal or complete). Ultrasound signs of PAS were recorded using the standardized description proposed by the EW-AIP including for grey scale imaging: loss of clear zone, myometrial thinning, the presence of placental lacunae; bladder wall interruption; placental bulge and focal exophytic mass and for CDI: utero-vesical hypervascularity; subplacental hypervascularity; bridging vessels and lacunae feeder vessels. Additional transabdominal and transvaginal sonographic (TVS) examinations of the placenta and cord insertion were performed at 28-30 weeks and 35-36 weeks when anomalies were identified at the 19-22 weeks scan.

Women with multiple pregnancies or requiring emergency delivery before 32 weeks were excluded from the study group. All patients were managed according to local protocols.

Patient's demographic data, previous obstetric and gynecological history, clinical findings, ultrasound data and images and symptoms at the time of the first examination were recorded and stored in a specialized database (Viewpoint Version 5, Bildverargeritung GmbH, Munich, Germany). All placentas were examined at delivery by the obstetric team and histopathological evaluation has been carried out when clinically indicated.

• Study Type: Observational
• Enrollment (Actual): 587

Contacts and Locations

Study Locations

• Italy
  • Bologna, Italy, 40138
    • IRCCS Azienda Ospedaliero-Universitaria di Bologna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

• Sampling Method: Probability Sample

Study Population

All patients with a singleton pregnancy conceived with IVF were consecutively recruited between 1st of May 2019 to 31st March 2021. Each case was matched with a control presenting with a SC during the same period of time.

All patients had antenatal care using a similar clinical protocol, which included at 11-14 weeks (nuchal thickness screening scan), 19-22 weeks (detailed fetal anatomy scan) and 33-35 weeks (growth scan).

Description

Inclusion Criteria:

• singleton pregnancies
• spontaneous pregnancies or pregnancies conceived with IVF

Exclusion Criteria:

• multiple pregnancies

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
spontaneous pregnancies	Diagnostic test: ultrasound according routine antenatal care; ultrasound examinations at 11-14, 19-22 and 33-35 weeks
pregnancies arising through IVF (homologus + hetereologus)	Diagnostic test: ultrasound according routine antenatal care; ultrasound examinations at 11-14, 19-22 and 33-35 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
type of placental and umbilical cord abnormalities	to identify which type of placental and umbilical cord abnormalities are more common in IVF singleton pregnancies	8 months
heterologous fertilization	to investigate if heterologous fertilization is an additional risk factor for the development of these abnormalities	8 months

Collaborators and Investigators

• Sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2019
• Primary Completion (Actual): March 31, 2021
• Study Completion (Actual): March 31, 2021

Study Registration Dates

• First Submitted: December 13, 2021
• First Submitted That Met QC Criteria: December 13, 2021
• First Posted (Actual): December 29, 2021

Study Record Updates

• Last Update Posted (Actual): February 14, 2022
• Last Update Submitted That Met QC Criteria: January 31, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pregnancy Complications; Placenta Diseases
• Other Study ID Numbers: 20/2019/Oss/AOUBo

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: we could share all IPD that underlie results in a publication

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No